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https://www.readbyqxmd.com/read/28177520/broad-spectrum-efficacy-with-ly2969822-an-oral-prodrug-of-metabotropic-glutamate-2-3-mglu2-3-receptor-agonist-ly2934747-in-rodent-pain-models
#1
Michael P Johnson, Mark A Muhlhauser, Eric S Nisenbaum, Rosa M A Simmons, Beth M Forster, Kelly L Knopp, Lijuan Yang, Denise Morrow, Dominic L Li, Jeffrey D Kennedy, Steven Swanson, James A Monn
BACKGROUND AND PURPOSE: A body of evidence suggests activation of metabotropic glutamate 2/3 (mGlu2/3 ) receptors would be an effective analgesic in chronic pain conditions. Thus, the analgesic properties of a novel mGlu2/3 receptor agonist prodrug were investigated. EXPERIMENTAL APPROACH: After oral absorption, the prodrug LY2969822 rapidly converts to the brain penetrant, potent, and subtype-selective mGlu2/3 receptor agonist LY2934747. Behavioral assessments of allodynia, hyperalgesia, or nocifensive behaviors in preclinical pain models were determined after administration of LY2969822 of 0...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28126369/neonatal-bladder-inflammation-induces-long-term-visceral-pain-and-altered-responses-of-spinal-neurons-in-adult-rats
#2
Pradeep Kannampalli, Reji Babygirija, Jiang Zhang, Michael M Poe, Guanguan Li, James M Cook, Reza Shaker, Banani Banerjee, Jyoti N Sengupta
Painful events early in life have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. However, the intrinsic mechanism is not well studied. We previously reported that neonatal bladder inflammation causes chronic visceral hypersensitivity along with molecular disruption of spinal GABAergic system in rats. The present study investigates whether these molecular changes affect the integrative function and responses of bladder-sensitive primary afferent and spinal neurons...
January 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28105664/visceral-and-somatic-pain-modalities-reveal-nav-1-7-independent-visceral-nociceptive-pathways
#3
James R F Hockley, Rafael González-Cano, Sheridan McMurray, Miguel A Tejada-Giraldez, Cian McGuire, Antonio Torres, Anna L Wilbrey, Vincent Cibert-Goton, Francisco R Nieto, Thomas Pitcher, Charles H Knowles, José Manuel Baeyens, John N Wood, Wendy J Winchester, David C Bulmer, Cruz Miguel Cendán, Gordon McMurray
Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV 1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor-specific NaV 1.7 knockout mouse (NaV 1.7(Nav1.8) ) and selective small-molecule NaV 1.7 antagonist PF-5198007. NaV 1.7(Nav1.8) mice showed normal nociceptive behaviours to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively...
January 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28096305/epithelial-expression-and-function-of-trypsin-3-in-irritable-bowel-syndrome
#4
Claire Rolland-Fourcade, Alexandre Denadai-Souza, Carla Cirillo, Cintya Lopez, Josue Obed Jaramillo, Cleo Desormeaux, Nicolas Cenac, Jean-Paul Motta, Muriel Larauche, Yvette Taché, Pieter Vanden Berghe, Michel Neunlist, Emmanuel Coron, Sylvain Kirzin, Guillaume Portier, Delphine Bonnet, Laurent Alric, Stephen Vanner, Celine Deraison, Nathalie Vergnolle
OBJECTIVES: Proteases are key mediators of pain and altered enteric neuronal signalling, although the types and sources of these important intestinal mediators are unknown. We hypothesised that intestinal epithelium is a major source of trypsin-like activity in patients with IBS and this activity signals to primary afferent and enteric nerves and induces visceral hypersensitivity. DESIGN: Trypsin-like activity was determined in tissues from patients with IBS and in supernatants of Caco-2 cells stimulated or not...
January 17, 2017: Gut
https://www.readbyqxmd.com/read/28079757/pathogenesis-of-abdominal-pain-in-bowel-obstruction-role-of-mechanical-stress-induced-upregulation-of-nerve-growth-factor-in-gut-smooth-muscle-cells
#5
You-Min Lin, Yu Fu, John Winston, Ravi Radhakrishnan, Sushil K Sarna, Li-Yen M Huang, Xuan-Zheng Shi
Abdominal pain is one of the major symptoms in bowel obstruction (BO); its cellular mechanisms remain incompletely understood. We tested the hypothesis that mechanical stress in obstruction upregulates expression of nociception mediator nerve growth factor (NGF) in gut smooth muscle cells (SMC), and NGF sensitizes primary sensory nerve to contribute to pain in BO. Partial colon obstruction was induced with a silicon band implanted in the distal bowel of Sprague-Dawley rats. Colon-projecting sensory neurons in the dorsal root ganglia (DRG, T13 to L2) were identified for patch clamp and gene expression studies...
January 6, 2017: Pain
https://www.readbyqxmd.com/read/28074518/editorial-increased-expression-of-nerve-growth-factor-correlates-with-visceral-hypersensitivity-and-impaired-gut-barrier-function-in-diarrhoea-predominant-irritable-bowel-syndrome-authors-reply
#6
EDITORIAL
https://www.readbyqxmd.com/read/28074514/editorial-increased-expression-of-nerve-growth-factor-correlates-with-visceral-hypersensitivity-and-impaired-gut-barrier-function-in-diarrhoea-predominant-irritable-bowel-syndrome
#7
EDITORIAL
S M P Bennet, H Törnblom
No abstract text is available yet for this article.
February 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28059627/structural-and-functional-alterations-in-the-colonic-microbiome-of-the-rat-in-a-model-of-stress-induced-irritable-bowel-syndrome
#8
Nicolaas H Fourie, Dan Wang, Sarah K Abey, Amy L Creekmore, Shuangsong Hong, Christiana G Martin, John W Wiley, Wendy A Henderson
Stress is known to perturb the microbiome and exacerbate irritable bowel syndrome (IBS) associated symptoms. Characterizing structural and functional changes in the microbiome is necessary to understand how alterations affect the biomolecular environment of the gut in IBS. Repeated water avoidance (WA) stress was used to induce IBS-like symptoms in rats. The colon-mucosa associated microbiome was characterized in 13 stressed and control animals by 16S sequencing. In silico analysis of the functional domains of microbial communities was done by inferring metagenomic profiles from 16S data...
January 2, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28039653/effect-of-ultrasound-guided-phrenic-nerve-block-on-shoulder-pain-after-laparoscopic-cholecystectomy-a-prospective-randomized-controlled-trial
#9
Myung Sub Yi, Won Joong Kim, Min Kyoung Kim, Hyun Kang, Yong-Hee Park, Yong Hun Jung, Seung Eun Lee, Hwa Yong Shin
BACKGROUND: Post-laparoscopic shoulder pain (PLSP) frequently follows a laparoscopic cholecystectomy. A proposed mechanism for PLSP is the irritation or injury of the phrenic nerve by the CO2 pneumoperitoneum during laparoscopic surgery. Here, we investigated whether a phrenic nerve block (PNB), performed under ultrasound guidance, could reduce the incidence and severity of PLSP after laparoscopic cholecystectomy. METHOD: Sixty patients were randomized into two groups, with one group receiving PNB with 4 ml (30 mg) of 0...
December 30, 2016: Surgical Endoscopy
https://www.readbyqxmd.com/read/28035535/the-role-of-the-gastrointestinal-microbiota-in-visceral-pain
#10
Kieran Rea, Siobhain M O'Mahony, Timothy G Dinan, John F Cryan
A growing body of preclinical and clinical evidence supports a relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and health status. Under normal homeostatic conditions this microbial population helps maintain intestinal peristalsis, mucosal integrity, pH balance, immune priming and protection against invading pathogens. Furthermore, these microbes can influence centrally regulated emotional behaviour through mechanisms including microbially derived bioactive molecules (amino acid metabolites, short-chain fatty acids, neuropeptides and neurotransmitters), mucosal immune and enteroendocrine cell activation, as well as vagal nerve stimulation...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28027594/neuroimmune-factors-in-functional-gastrointestinal-disorders-a-focus-on-irritable-bowel-syndrome
#11
REVIEW
G E Boeckxstaens, M M Wouters
BACKGROUND: Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders (FGIDs). Visceral pain stimuli are perceived and transmitted by afferent neurons residing in the dorsal root ganglia that have sensory nerve endings in the gut wall and mesentery. Accumulating evidence indicates that peripheral activation and sensitization of these sensory nerve endings by bioactive mediators released by activated immune cells, in particular mast cells, can lead to aberrant neuroimmune interactions and the development and maintenance of visceral hypersensitivity...
December 27, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27997083/acute-sacral-nerve-stimulation-reduces-visceral-mechanosensitivity-in-a-cross-organ-sensitization-model
#12
L D Langlois, E Le Long, M Meleine, M Antor, K Atmani, P Dechelotte, A M Leroi, G Gourcerol
BACKGROUND: Sacral nerve stimulation (SNS) is a surgical treatment of fecal and urinary incontinence that consists of inserting a stimulating electrode into one of the s3 or s4 sacral holes. In addition to the benefit of SNS in the treatment of incontinence, recent studies showed that SNS is effective in the treatment of irritable bowel syndrome as well as bladder pain syndrome. The aim of this study was to evaluate the effect of SNS on visceral mechanosensitivity in a cross-organ sensitization rat model...
November 7, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27956200/anatomic-relationships-of-the-pelvic-autonomic-nervous-system-in-female-cadavers-clinical-applications-to-pelvic%C3%A2-surgery
#13
Christopher M Ripperda, Lindsey A Jackson, John N Phelan, Kelley S Carrick, Marlene M Corton
BACKGROUND: The integrity of the pelvic autonomic nervous system is essential for proper bowel, bladder, and sexual function. OBJECTIVE: The purpose of this study was to characterize the anatomic path of the pelvic autonomic system and to examine relationships to clinically useful landmarks. STUDY DESIGN: Detailed dissections were performed in 17 female cadavers. Relationships of the superior hypogastric plexus to aortic bifurcation and midpoint of sacral promontory were examined; the length and width of plexus was documented...
December 9, 2016: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/27916557/histone-acetylation-and-histone-deacetylation-in-neuropathic-pain-an-unresolved-puzzle
#14
REVIEW
Ravneet Kaur Khangura, Anjana Bali, Amteshwar Singh Jaggi, Nirmal Singh
Chronic pain is broadly classified into somatic, visceral or neuropathic pain depending upon the location and extent of pain perception. Evidences from different animal studies suggest that inflammatory or neuropathic pain is associated with altered acetylation and deacetylation of histone proteins, which result in abnormal transcription of nociceptive processing genes. There have been a number of studies indicating that nerve injury up-regulates histone deacetylase enzymes, which leads to increased histone deacetylation and induce chronic pain...
December 2, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27913002/clinical-evaluation-and-management-of-radiation-fibrosis-syndrome
#15
REVIEW
Michael D Stubblefield
Radiation fibrosis syndrome describes the multiple neuromuscular, musculoskeletal, visceral, and other late effects that result from radiation-induced fibrosis. Radiation can damage the spinal cord, nerve roots, plexus, local peripheral nerves, and muscles within the radiation field. This constellation is known as a "myelo-radiculo-plexo-neuro-myopathy" and can result in pain, sensory loss, weakness, and other signs and symptoms. Although there is no curative treatment for radiation damage, supportive management of symptoms can be helpful in restoring and maintaining function and quality of life...
February 2017: Physical Medicine and Rehabilitation Clinics of North America
https://www.readbyqxmd.com/read/27905561/anti-hu-antibodies-activate-enteric-and-sensory-neurons
#16
Qin Li, Klaus Michel, Anita Annahazi, Ihsan E Demir, Güralp O Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio, Michael Schemann
IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899695/consistent-sex-dependent-effects-of-pkm%C3%AE-gene-ablation-and-pharmacological-inhibition-on-the-maintenance-of-referred-pain
#17
Hibatulnaseer Nasir, Hicham Mahboubi, Sandeep Gyawali, Stephanie Ding, Aiste Mickeviciute, J Vaigunda Ragavendran, André Laferrière, Ursula Stochaj, Terence J Coderre
BACKGROUND: Persistently active PKMζ has been implicated in maintaining spinal nociceptive sensitization that underlies pain hypersensitivity. However, evidence for PKMζ in the maintenance of pain hypersensitivity comes exclusively from short-term studies in males using pharmacological agents of questionable selectivity. The present study examines the contribution of PKMζ to long-lasting allodynia associated with neuropathic, inflammatory, or referred visceral and muscle pain in males and females using pharmacological inhibition or genetic ablation...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27896830/vagal-nerve-endings-in-visceral-pleura-and-triangular-ligaments-of-the-rat-lung
#18
Feng-Bin Wang, Yi-Han Liao, Yao-Chen Wang
The inner thoracic cavity is lined by the parietal pleura, and the lung lobes are covered by the visceral pleura. The parietal and visceral plurae form the pleural cavity that has negative pressure within to enable normal respiration. The lung tissues are bilaterally innervated by vagal and spinal nerves, including sensory and motor components. This complicated innervation pattern has made it difficult to discern the vagal vs. spinal processes in the pulmonary visceral pleura. With and without vagotomy, we identified vagal nerve fibres and endings distributed extensively in the visceral pleura ('P'-type nerve endings) and triangular ligaments ('L'-type nerve endings) by injecting wheat germ agglutinin-horseradish peroxidase as a tracer into the nucleus of solitary tract or nodose ganglion of male Sprague-Dawley rats...
November 29, 2016: Journal of Anatomy
https://www.readbyqxmd.com/read/27876359/somatoautonomic-reflexes-in-acupuncture-therapy-a-review
#19
Sae Uchida, Fusako Kagitani, Ikuko Sato-Suzuki
Oriental therapies such as acupuncture, moxibustion, or Anma, have been used to treat visceral disorders since ancient times. In each of these therapies, stimulation of the skin or underlying muscles leads to excitation of afferent nerves. The sensory information is carried to the central nervous system, where it is transferred to autonomic efferents, thus affecting visceral functions. This neuronal pathway, known as the "somatoautonomic reflex", has been systematically studied by Sato and his colleagues for over a half century...
November 16, 2016: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/27862119/increased-expression-of-nerve-growth-factor-correlates-with-visceral-hypersensitivity-and-impaired-gut-barrier-function-in-diarrhoea-predominant-irritable-bowel-syndrome-a-preliminary-explorative-study
#20
X J Xu, Y L Zhang, L Liu, L Pan, S K Yao
BACKGROUND: Neural-immune-endocrine network mechanism has attracted increased attention in diarrhoea-predominant irritable bowel syndrome (IBS-D). Pre-clinical evidence indicates that nerve growth factor (NGF) mediates visceral hypersensitivity and gut barrier dysfunction, via interactions with mast cells and sensory nerve fibres. AIM: To explore the role of nerve growth factor, as well as mast cell-nerve growth factor-nerve interaction in IBS-D pathophysiology...
January 2017: Alimentary Pharmacology & Therapeutics
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